New process for the preparation of pristinamycin IIB derivatives

Abstract

Pristinamycin II B derivatives of formula I in which R represents: ##STR1## either a 4- to 7-membered nitrogen-containing heterocyclic radical, optionally containing 1 or more other hetero atoms chosen from nitrogen, oxygen and sulphur in the sulphoxide or sulphone form, and unsubstituted or substituted by alkyl, or alkyl of 2 to 4 carbon atoms, substituted by 1 or 2 radicals chosen from phenyl, cycloalkylamino or N-alkyl-N-cycloalkylamino having 3 to 6 ring carbon atoms, alkylamino, dialkylamino or dialkylcarbamoyloxy (the alkyl parts of these last 2 radicals being optionally joined to form, with the nitrogen atom to which they are attached, a 4- to 7-membered saturated or unsaturated heterocycle optionally containing another hetero atom chosen from nitrogen, oxygen and sulphur in the sulphoxide or sulphone form, and unsubstituted or substituted by alkyl) or a said alkyl substituted by one or more 4- or 7-membered nitrogen-containing heterocycles optionally containing 1 or 2 other hetero atoms chosen from nitrogen, oxygen and sulphur in the sulphoxide or sulphone form and unsubstituted or substituted by an alkyl radical, the said heterocycles being attached to the alkyl via a carbon atom, at least one of the substituents carried by the alkyl being a nitrogen-containing substituent capable of forming salts, or a [(S)-1-methyl-2-pyrrolidinyl]methyl radical, the aforesaid alkyl radicals being straight-chain or branched and containing, unless otherwise stated, 1 to 10 carbon atoms each, including isomeric forms thereof and mixtures thereof, and the salts thereof, are made by oxidizing a pristinamycin II B derivative of formula II ##STR2## with potassium peroxymonosulphate.

We claim: 
     
       1. A process for the preparation of a pristinamycin II B  of formula: ##STR22## in which R represents either a heterocyclic radical chosen from 3-azetidinyl, 3-pyrrolidinyl, 3- or 4-piperidyl, or 3- or 4-azepinyl, and unsubstituted or substituted by alkyl, or alkyl of 2 to 4 carbon atoms, substituted by 1 or 2 radicals chosen from phenyl, cycloalkylamino having 3 to 6 ring carbon atoms or N-alkyl-N-cycloalkylamino having 3 to 6 ring carbon atoms, alkylamino, dialkylamino or dialkylcarbamoyloxy (the alkyl parts of these last 2 radicals being optionally joined to form, with the nitrogen atom to which they are attached, a heterocyclic radical chosen from 1-azetidinyl, 1-pyrrolidiyl, piperidino, 1-azepinyl, morpholino, thiomorpholino in the sulphoxide or sulphone form, 1-piperazinyl, 4-alkyl-1-piperazinyl, N-alkyl-1-homopiperazinyl, or 1-imidazolyl, and unsubstituted or substituted by alkyl) or a said alkyl substituted by a heterocyclic radical chosen from 2-azetidinyl, 2-pyrrolidinyl, 2-piperidyl, 2-azepinyl, piperazinyl, 4-alkyl-piperazinyl, quinolyl, isoquinonlyl, or imidazolyl, and unsubstituted or substituted by alkyl, the said heterocyclic radicals being attached to the alkyl via a carbon atom, at least one of the substituents carried by the alkyl being a nitrogen-containing substituent capable of forming salts,   or a (S)-1-methyl-2-pyrrolidinyl)methyl radical, the aforesaid alkyl radicals being straight-chain or branched and containing, unless otherwise stated, 1 to 10 carbon atoms each, including isomeric forms thereof and mixtures thereof, and its acid addition salts,   which comprises oxidizing a pristinamycin II B  (or a salt or protected form thereof) of formula: ##STR23##  in which R is as defined above, it being understood that where R contains a thiomorpholino radical, the sulphur atom may be in the form of sulphide, sulphoxide or sulphone, with potassium peroxymonosulphate, and optionally separating the product obtained into its isomers and, if necessary, removing any protective radical and optionally converting the product obtained into an acid addition salt.   
     
     
       2. Process according to claim 1 in which the oxidation is carried out in an aqueous medium at -60° to +25° C. 
     
     
       3. Process according to claim 1 in which R is alkyl of 2 to 4 carbon atoms substituted by dialkylamino in which each alkyl has 1 to 4 carbon atoms.